1 Five million central venous catheters (CVCs) are inserted into patients in the US each year and up to 2 500,000 result in bloodstream infections with medical remediation costs ranging between $4,000 - 3 $28,000 for each incidence or $2 to $14 billion annually.1, 2 Even more alarming is that roughly 25,000 of 4 these CVC infections lead to fatalities. Since October 2008, the U.S. Centers for Medicare and Medicaid 5 Services no longer reimburse hospitals for cost incurred by CVC-associated infections despite the fact 6 that CVC infections continue to increase year over year. The rise in the number of infections coupled with 7 the emergence of antibiotic resistant bacteria has resulted in an urgent need for new antimicrobial 8 therapies. The purpose of this project is to develop a nitric oxide (NO) releasing CVC coating that exhibits 9 broad-spectrum antimicrobial activity via NO released from the device surface, which, if successful, will be 10 a cost-effective solution for preventing these CVC infections. 11 Current scientific knowledge regarding NO's role in immune system response and its proven broad- 12 spectrum antimicrobial activity suggest that NO release therapies may represent a vastly improved 13 methodology for preventing medical device infections. With Phase I funding, Novan will use its proprietary 14 NO-releasing particle technology to develop a novel NO-releasing antimicrobial catheter coating. This 15 platform technology overcomes the challenges associated with the storage and controlled delivery of the 16 gaseous NO species that have hindered the development of NO-releasing devices. 17 Through this 1-year, Phase I SBIR the Company expects to:1) develop polyurethane-based catheter 18 coatings that release NO from both the internal and external device surface, and 2) demonstrate the in 19 vitro antimicrobial activity of the NO-releasing catheter materials against representative organisms 20 relevant to catheter-related blood stream infections. Novan will conduct the particle synthesis, 21 polyurethane formulation works, catheter dip-coating procedures, and the evaluation of microbial 22 colonization and biofilm formation on prototype catheter segments. Following the completion of Phase I 23 milestones, Novan will begin preclinical evaluation of the NO-releasing device in animal models of 24 infections during Phase II and complete the necessary pre-clinical safety and medical device performance 25 testing required for FDA submission as a medical device. PUBLIC HEALTH RELEVANCE: Five million central venous catheters (CVCs) are inserted into patients in the US each year and up to 500,000 result in bloodstream infections with medical remediation costs ranging between $4,000 - $28,000 for each incidence or $2 to $14 billion annually.1, 2 Even more alarming is that roughly 25,000 of these CVC infections lead to fatalities. The purpose of this project is to develop a nitric oxide (NO) releasing CVC coating that exhibits broad-spectrum antimicrobial activity via NO-released from the device surface to vastly improve the prevention of medical device infections and significantly reduce associated healthcare costs.